Method for treatment of reactive arthritis or bursitis

ABSTRACT

A method for treatment for conditions in human beings associated with either or both reactive arthritis or bursitis comprising administering a combination of member of the family of synthetic purine nucleoside analog antiviral drugs, a member of the tetracycline family, and a member of the nitroimidazole family, or alternatively, administering a combination of a member of the family of synthetic purine nucleoside analog antiviral drugs, a member of the quinolone family, and a member of the nitroimidazole family.

This is a continuation of application Ser. No. 10/896,612 filed Jul. 20,2004, still pending, which was a continuation of application Ser. No.10/271,117 filed Oct. 15, 2002, now U.S. Pat. No. 6,765,000, which was acontinuation of application Ser. No. 09/510,704, filed Feb. 22, 2000,now U.S. Pat. No. 6,465,473, which was a continuation-in-part ofapplication Ser. No. 09/270,962, filed Mar. 17, 1999, now U.S. Pat. No.6,087,382.

BACKGROUND OF THE INVENTION

This invention relates to an improved method for treatment of symptomsassociated in humans with reactive arthritis or idiopathic bursitis.

Reactive arthritis refers to a spondyloarthritity which usually arisesas a complication of an infection elsewhere in the body. Reactivearthritis can be caused by species of Shigella bacteria (most notablyShigella flexneri), Yersinia enterocolitica, Campylobacter jejuni,several species of Salmonella, genitourinary pathogens, Chlamydiatrachomatis, Neisseria gonorrhea, Ureaplasma urealyticum, Streptococcuspyogenes, and other yet unidentified infectious agents.

Reactive arthritis commonly occurs in young men and women, but can occurat any age. Sufferers experience joint pain, stiffness, redness orswelling. Common symptoms may include fatigue, malaise, fever, andweight loss. The joints of the lower extremities, including the knee,ankle, and joints of the foot, are the most common sites of involvement,but symptoms can also occur in the wrists, fingers, elbows, shoulders,neck, and lower back. Other symptoms may include urethritis andprostatitis in males, and cervicitis or salpingitis in females. Oculardisease is common ranging from transient, asymptomatic conjunctivitis toaggressive anterior uveitis that occasionally results in blindness.Mucocutaneous lesions and nail changes are frequent. On less frequent orrare occasions manifestations of reactive arthritis include cardiacconduction defects, aortic insufficiency, central or peripheral nervoussystem lesions, and pleuropulmonary infiltrates.

Treatment of patients suffering from reactive arthritis withnonsteroidal anti-inflammatory drugs (“NSAIDs”) provides some benefit,although symptoms of reactive arthritis are rarely completely alleviatedand some patients fail to respond at all. The preferred initialtreatment of choice for acute reactive arthritis is indomethacin individed doses of 75 to 150 milligrams per day. The NSAID of last resortis phenylbutazone, in doses of 100 milligrams twice or three times perday, because of its potentially serious side effects. Patients withdebilitating symptoms refractory to NSAID therapy may be treated withcytotoxic agents such as azathioprine or methotrexate, or withsulfasalazine. Tendinitis, other lesions, and uveitis may benefit fromcorticosteroids. Minocycline hydrochloride, a semisynthetic derivativeof tetracycline, is indicated for infections caused by at least Shigellamicroorganisms, Streptococcus pyogenes, and Neisserie gonorrhoeae. It istherefore an accepted treatment in incidents of reactive arthritistriggered by these biological entities.

Long-term follow-up studies have suggested that some joint symptomspersist in many, if not most, patients with reactive arthritis.Recurrences of the more acute symptoms are common and as many astwenty-five percent of patients either become unable to work or areforced to change occupations because of persistent joint problems.

Bursitis is inflammation of a bursa, a thin-walled sac lined withsynovial tissue. The function of the bursa is to facilitate movement oftendons and muscles over bony prominences. Bursitis may be caused byexcessive frictional forces, trauma, systemic disease such as rheumatoidarthritis or gout, or infection. The most common form of bursitis issubacromial. Trochanteric bursitis causes patients to experience painover the lateral aspect of the hip and upper thigh, and tenderness overthe posterior aspect of the greater trochanter. Retrocalcaneal bursitisinvolves the bursa located between the calcaneus and the posteriorsurface of the Achilles tendon. Pain is experienced at the back of theheel, and swelling appears on either or both of the medial and lateralsides of the tendon. Retrocalcaneal bursitis occurs in association withspondyloarthritities, rheumatoid arthritis, gout, and trauma.

Treatment of bursitis generally consists of prevention of theaggravating condition, rest of the involved part, an NSAID, and localsteroid injection. In the long term, bursitis can result in loss of useof a joint and chronic pain syndrome.

The long term effects of reactive arthritis and bursitis range fromchronic pain to crippling disability. It is also thought that manyinstances of osteoarthritis and psoriatic arthritis are in actualityreactive arthritis. Unfortunately, current procedures for managementtreat the symptoms of these diseases rather than their underlyingpathogens.

SUMMARY OF THE INVENTION

Significant benefits can be obtained by treating humans affected withconditions associated with reactive arthritis or bursitis usingcombinations of acyclovir, minocycline hydrochloride, and metronidazoleor, alternatively, valacyclovir hydrochloride, minocyclinehydrochloride, and metronidazole.

Acyclovir is an anti-viral drug. The chemical name of acyclovir is2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one.Acyclovir is commercially available under the brand name ZOVIRAX® incapsules, tablets, or suspension. Acyclovir has demonstrated anti-viralactivity against herpes simplex virus types I and II, varicella-zostervirus, Epstein-Barr virus and cytomegalovirus, both in vitro and invivo.

Valacyclovir hydrochloride (sold under the brand name Valtrex®) is thehydrochloride salt of L-valyl ester of acyclovir. The chemical name ofvalacyclovir hydrochloride is L-valine2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester,monohydrochloride. Valacyclovir hydrochloride is rapidly and nearlycompletely converted to acyclovir in the body.

Acyclovir and valacyclovir hydrochloride are members of the family ofsynthetic purine nucleoside analog antiviral drugs.

Minocycline hydrochloride is a bacteriostatic antibiotic which exertsits antimicrobial effect by inhibition of bacterial protein synthesis.It has been shown to be effective against gram-negative bacteria, somegram-positive bacteria and other microorganisms. Minocyclinehydrochloride is a member of the tetracycline family.

Metronidazole is an oral synthetic antiprotozoal and antibacterialagent. Heretofore it has been indicated for treatment of symptomatictrichomoniasis, intestinal amebiasis, and a wide range ofintra-abdominal, skin, gynecological, bone and joint, lower respiratorytract and central nervous system infections, bacterial septicemia andendocarditis. Metronidazole is a member of the nitroimidazole family.

Ciprofloxacin is a member of the quinolone family of antimicrobialagents. It is a bacteriacidal antibiotic, in the class of antibioticscalled fluoroquinolones, which acts to interfere with DNA gyrase, anenzyme needed for the synthesis of bacterial DNA. Quinolones are widelyconsidered to be a medically acceptable alternative to tetracyclines.

One embodiment of a combination for treatment of the symptoms in humanbeings of reactive arthritis or idiopathic bursitis, or both, comprisesthe combination of acyclovir, minocycline hydrochloride, andmetronidazole. An alternative combination comprises the substitution ofvalacyclovir hydrochloride in place of acyclovir. The pharmaceuticaldosages of the compounds of the combination may be administered incapsules, tablets, in suspension form, or by injection.

The invention provides a method for administration of a pharmaceuticalcombination that puts the diseases of reactive arthritis and bursitisinto remission. Treatment with the combination may effect a cure ofreactive arthritis and bursitis, but definitive testing has not beenperformed to confirm that fact.

It is therefore a primary object of the invention to provide a methodfor administration of a combination for treating conditions in humanbeings associated with either or both reactive arthritis or idiopathicbursitis.

Another object of the invention is to provide a method foradministration of a treatment for conditions in human beings associatedwith either or both reactive arthritis or idiopathic bursitis that putsthe disease being treated into fill remission.

A further object of the invention is to provide a method foradministration of a treatment for any constellation of symptoms amenableto treatment using the above combination, including for example, casesof reactive arthritis which have been misdiagnosed as osteoarthritis orpsoriatic arthritis.

DETAILED DESCRIPTION OF THE INVENTION

U.S. Pat. No. 6,087,382 to Bonner, Jr., et al., describes a method oftreatment involving administration of a combination of L-lysine,minocycline hydrochloride, and metronidazole. An alternate methodincludes administration of InH for those individuals who have testedpositively for mycobacterial exposure, along with the underlyingcombination of L-lysine, minocycline hydrochloride, and metronidazole.Another method described in U.S. Pat. No. 6,465,473 to Bonner, Jr., etal., includes administration of valacyclovir hydrochloride with theunderlying combination of L-lysine, minocycline hydrochloride, andmetronidazole. A third method of treatment, described in applicants'U.S. Pat. No. 6,197,776, includes administration of acyclovir with theunderlying combination of L-lysine, minocycline hydrochloride, andmetronidazole. An embodiment of the treatment, described in applicants'U.S. Pat. No. 6,765,000, comprises a pharmaceutical combinationincluding acyclovir, minocycline hydrochloride, and metronidazole.Alternatively, the treatment may include valacyclovir hydrochloride,minocycline hydrochloride, and metronidazole. Either of theseembodiments may be supplemented with administration of pyridoxinehydrochloride, glucosamine, manganese, vitamin C, and desalinatedseawater, such as Essence of Life.

Administration will generally be accomplished orally via capsules,tablets, or in suspension form, but delivery could be accomplished byinjection, or any other method commonly used for administration ofinternal medicines.

Like L-lysine, acyclovir inhibits herpes simplex viruses, but by adifferent mechanism. While L-lysine tends to stop the virus fromreplicating by inhibiting the initiation of the replication process,acyclovir inhibits effective replication of actively replicating viralparticles, e.g., by stopping replication of herpes viral DNA. This isaccomplished by either competitive inhibition or inactivation of viralDNA polymerase or incorporation and termination of the growing viral DNAchain. It is believed that acyclovir results in a substantial benefitdue to its inhibition of virus replication. In double-blind testing, ithas been found that the administration of the combination of acyclovir,minocycline hydrochloride, and metronidazole is an effective treatmentfor reactive arthritis or bursitis. Acyclovir has never been used in theprior art for treatment of arthritis or bursitis. It does not appear tobe effective alone for the treatment of these diseases. The preferreddose of acyclovir is 400 mg twice daily. The daily dose of acyclovir mayvary from 200 mg to 4 grams.

The preferred dose of valacyclovir hydrochloride is 500 mg twice daily.The total daily dose of valacyclovir hydrochloride may vary from 125 mgto 4 grams.

The preferred dose of minocycline hydrochloride is an initial dosage of200 mg followed by doses of 100 mg twice per day. Daily doses ofminocycline hydrochloride following the initial administration of 200 mgmay vary from 50 mg to 200 mg. Based upon their similar properties, itis expected that other members of the tetracycline family such asdoxycycline can be effectively substituted, in the combination, forminocycline hydrochloride.

The preferred dose of metronidazole is 250-500 mg twice per day. Thetotal dose per day of metronidazole may vary from 100 mg to 1,000 mg.

It is known that the combination of minocycline hydrochloride, InH, andmetronidazole inhibits the multiplication of susceptible organisms,including shigella, salmonella, chlamydia, streptococci, andmycobacteria. Applicants have also determined that the combination ofL-lysine, minocycline hydrochloride, and metronidazole provides amedically effective treatment for reactive arthritis and bursitis. SeeU.S. Pat. No. 6,087,382. It has also been shown that the combination ofacyclovir, L-lysine, minocycline hydrochloride, and metronidazoleprovides an effective treatment for these conditions. See U.S. Pat. No.6,197,776. Individuals with severe symptoms, including joint swellingand joint contractures, who were not thought to be candidates fortreatment using the combination of L-lysine, minocycline hydrochloride,and metronidazole only, have also experienced substantial beneficialeffects in response to treatment with that combination and valacyclovirhydrochloride.

The preferred embodiment of the present invention comprises thecombination of acyclovir, or its prodrug valacyclovir hydrochloride,with minocycline hydrochloride and metronidazole. An alternateembodiment comprises valacyclovir hydrochloride with minocyclinehydrochloride and metronidazole. These combinations each provide amedically effective treatment for reactive arthritis and bursitis. Thetotal combination of medicines in each of these embodiments presents abroad spectrum approach that it is believed effectively addresses theunderlying pathogenesis for reactive arthritis and what has previouslybeen referred to as idiopathic bursitis, and further is a beneficialtreatment for reactive arthritis in particular cases wherein the symptomcomplex has been misdiagnosed as osteoarthritis or psoriatic arthritis,or in any other similar cases of misdiagnosis.

EXAMPLE

The following examples serve to illustrate the invention, but is notmeant to restrict its effective scope.

Example 1

A 77 year old female presented with complaints of neck, upper back,lower back, bilateral shoulder, bilateral wrist, digits of hands,bilateral hip, and bilateral ankle pains of years duration. The patientcomplained of associated stiffness in those same joints. Her physicalexamination was remarkable for tenderness at her neck, right shoulder,elbow bilaterally, wrist bilaterally, the metacarpal phalangeal and theproximal interphalangeal joints of her right hand, hip bilaterally, kneebilaterally, and the Achilles insertion area bilaterally. The Sed rateand rheumatoid factors were normal. This patient was diagnosed withreactive arthritis and was started on a treatment consisting of 125 mgof metronidazole, 250 mg of valacyclovir hydrochloride, and 50 mg ofminocycline hydrochloride twice daily. After 69 days of such treatment,the patient noted pain in the palm of her left hand only. She furtherdenied any stiffness. Physical examination on the 69^(th) day did notreveal any tenderness. Thus, treatment effected resolution of pain,stiffness, and tenderness in this patient.

Example 2

A 52 year old male presented with complaints of bilateral knee and leftwrist pain. He also noted associated morning stiffness. He was treatedwith minocyline hydrochloride 100 mg BID and acyclovir 400 mg BID. Thisresulted in significan improvement, but not total resolution of hiscomplaints of pain and stiffness in his knees and left wrist.

There have been thus described certain preferred embodiments of apharmaceutical formulation for treatment of conditions in human beingsassociated with either or both reactive arthritis or idiopathicbursitis. While preferred embodiments have been described and disclosed,it will be recognized by those with skill in the art that modificationsare within the true scope and spirit of the invention. The appendedclaims are intended to cover all such modifications.

1. A method for medically treating the symptoms of reactive arthritis orbursitis in humans comprising: administering to a patient an effectiveamount of the combination of a member of the family of synthetic purinenucleoside analog antiviral drugs or a pharmaceutically acceptable esteror a metabolite thereof, a member of the tetracycline family or ametabolite thereof, and a member of the nitroimidazole family or ametabolite thereof.
 2. The method for treatment of claim 1 wherein: saidmember of the family of synthetic purine nucleoside analog antiviraldrugs comprises acyclovir.
 3. The method for treatment of claim 1wherein: said member of the family of synthetic purine nucleoside analogantiviral drugs comprises valacyclovir.
 4. The method for treatment ofclaim 1 wherein: said member of the tetracycline family comprisesminocycline hydrochloride.
 5. The method for treatment of claim 1wherein: said member of the nitroimidazole family comprisesmetronidazole.
 6. The method for treatment of claim 1 wherein: saidmember of the family of synthetic purine nucleoside analog antiviraldrugs comprises acyclovir or a pharmaceutically acceptable esterthereof, said member of the tetracycline family comprises minocyclinehydrochloride, and said member of the nitroimidazole family comprisesmetronidazole.
 7. The treatment of claim 6 wherein: betweenapproximately 50 to 200 mg of minocycline hydrochloride areadministered.
 8. The treatment of claim 6 wherein: between approximately100 mg to 4 gm of acyclovir are administered.
 9. The treatment of claim6 wherein: between approximately 100 mg to 1 gm of metronidazole areadministered.
 10. The treatment of claim 6 wherein: betweenapproximately 100 mg to 4 gm of acyclovir are administered, betweenapproximately 50 to 200 mg of minocycline hydrochloride areadministered, and between approximately 100 mg to 1 gm of metronidazoleare administered.
 11. The treatment of claim 6 wherein: approximately400 mg of acyclovir are administered twice daily.
 12. The treatment ofclaim 6 wherein: approximately 100 mg of minocycline hydrochloride areadministered twice daily.
 13. The treatment of claim 6 wherein:approximately 250 mg of metronidazole are administered twice daily. 14.The treatment of claim 6 wherein: approximately 400 mg of acyclovir areadministered twice daily, approximately 100 mg of minocyclinehydrochloride are administered twice daily, and approximately 250 mg ofmetronidazole are administered twice daily.
 15. The method for treatmentof claim 1 wherein: said member of the family of synthetic purinenucleoside analog antiviral drugs comprises valacyclovir or apharmaceutically acceptable ester thereof, said member of thetetracycline family comprises minocycline hydrochloride, and said memberof the nitroimidazole family comprises metronidazole.
 16. The treatmentof claim 15 wherein: between approximately 125 mg to 4 gm ofvalacyclovir hydrochloride are administered daily.
 17. The treatment ofclaim 15 wherein: between approximately 50 to 200 mg of minocyclinehydrochloride are administered daily.
 18. The treatment of claim 15wherein: between approximately 100 mg to 1 gm of metronidazole areadministered daily.
 19. The treatment of claim 15 wherein: betweenapproximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered daily, between approximately 50 to 200 mg of minocyclinehydrochloride are administered daily, and between approximately 100 mgto 1 gm of metronidazole are administered daily.
 20. The treatment ofclaim 15 wherein: approximately 500 mg of valacyclovir hydrochloride areadministered twice daily.
 21. The treatment of claim 15 wherein:approximately 100 mg of minocycline hydrochloride are administered twicedaily.
 22. The treatment of claim 15 wherein: approximately 250 mg ofmetronidazole are administered twice daily.
 23. The treatment of claim15 wherein: approximately 500 mg of valacyclovir hydrochloride areadministered twice daily, approximately 100 mg of minocyclinehydrochloride are administered twice daily, and approximately 250 mg ofmetronidazole are administered twice daily.
 24. A method for medicallytreating the symptoms of reactive arthritis or bursitis in humanscomprising: administering to a patient an effective amount of thecombination of a member of the family of synthetic purine nucleosideanalog antiviral drugs or a pharmaceutically acceptable ester or ametabolite thereof, a member of the quinolone family or a metabolitethereof, and a member of the nitroimidazole family or a metabolitethereof.
 25. The method for treatment of claim 24 wherein: said memberof the family of synthetic purine nucleoside analog antiviral drugscomprises acyclovir.
 26. The method for treatment of claim 24 wherein:said member of the family of synthetic purine nucleoside analogantiviral drugs comprises valacyclovir hydrochloride.
 27. The method fortreatment of claim 24 wherein: said member of the quinolone familycomprises Ciprofloxacin.
 28. The method for treatment of claim 24wherein: said member of the nitroimidazole family comprisesmetronidazole.
 29. The method for treatment of claim 1 wherein: saidmember of the family of synthetic purine nucleoside analog antiviraldrugs comprises acyclovir or a pharmaceutically acceptable esterthereof, said member of the quinolone family comprises Ciprofloxacin,and said member of the nitroimidazole family comprises metronidazole.30. The treatment of claim 29 wherein: between approximately 50 mg to 2gm of Ciprofloxacin are administered.
 31. The treatment of claim 29wherein: between approximately 100 mg to 4 gm of acyclovir areadministered.
 32. The treatment of claim 29 wherein: betweenapproximately 100 mg to 1 gm of metronidazole are administered.
 33. Thetreatment of claim 29 wherein: between approximately 100 mg to 4 gm ofacyclovir are administered, between approximately 50 mg to 2 gm ofCiprofloxacin are administered, and between approximately 100 mg to 1 gmof metronidazole are administered.
 34. The treatment of claim 29wherein: approximately 400 mg of acyclovir are administered twice daily.35. The treatment of claim 29 wherein: approximately 500 mg ofCiprofloxacin are administered twice daily.
 36. The treatment of claim29 wherein: approximately 250 mg of metronidazole are administered twicedaily.
 37. The treatment of claim 29 wherein: approximately 400 mg ofacyclovir are administered twice daily, approximately 500 mg ofCiprofloxacin are administered twice daily, and approximately 250 mg ofmetronidazole are administered twice daily.
 38. The method for treatmentof claim 24 wherein: said member of the family of synthetic purinenucleoside analog antiviral drugs comprises valacyclovir or apharmaceutically acceptable ester thereof, said member of the quinolonefamily comprises Ciprofloxacin, and said member of the nitroimidazolefamily comprises metronidazole.
 39. The treatment of claim 38 wherein:between approximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered daily.
 40. The treatment of claim 38 wherein: betweenapproximately 50 mg to 2 gm of Ciprofloxacin are administered daily. 41.The treatment of claim 38 wherein: between approximately 100 mg to 1 gmof metronidazole are administered daily.
 42. The treatment of claim 38wherein: between approximately 125 mg to 4 gm of valacyclovirhydrochloride are administered daily, between approximately 50 mg to 2gm of Ciprofloxacin are administered daily, and between approximately100 mg to 1 gm of metronidazole are administered daily.
 43. Thetreatment of claim 38 wherein: approximately 500 mg of valacyclovirhydrochloride are administered twice daily.
 44. The treatment of claim38 wherein: approximately 500 mg of Ciprofloxacin are administered twicedaily.
 45. The treatment of claim 38 wherein: approximately 250 mg ofmetronidazole are administered twice daily.
 46. The treatment of claim38 wherein: approximately 500 mg of valacyclovir hydrochloride areadministered twice daily, approximately 500 mg of Ciprofloxacin areadministered twice daily, and approximately 250 mg of metronidazole areadministered twice daily.
 47. The method for treatment of claim 24wherein: said member of the family of synthetic purine nucleoside analogantiviral drugs comprises acyclovir or a pharmaceutically acceptableester thereof, said member of the quinolone family comprises afluoroquinolone, and said member of the nitroimidazole family comprisesmetronidazole.
 48. The treatment of claim 29 wherein: saidpharmaceutically acceptable ester of acyclovir is valacyclovirhydrochloride.
 49. The treatment of claim 48 wherein: betweenapproximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered daily.
 50. The treatment of claim 48 wherein: betweenapproximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered, between approximately 50 mg to 2 gm of Ciprofloxacin areadministered, and between approximately 100 mg to 1 gm of metronidazoleare administered.
 51. The treatment of claim 48 wherein: approximately500 mg of valacyclovir hydrochloride are administered twice daily.
 52. Amethod for medically treating the symptoms of reactive arthritis orbursitis in humans comprising: administering to a patient an effectiveamount of the combination of a member of the family of synthetic purinenucleoside analog antiviral drugs or a pharmaceutically acceptable esteror a metabolite thereof, and a member of the tetracycline family or ametabolite thereof.
 53. The method for treatment of claim 52 wherein:said member of the family of synthetic purine nucleoside analogantiviral drugs comprises acyclovir.
 54. The treatment of claim 53wherein: between approximately 100 mg to 4 gm of acyclovir areadministered.
 55. The treatment of claim 54 wherein: approximately 400mg of acyclovir are administered twice daily.
 56. The method fortreatment of claim 52 wherein: said member of the family of syntheticpurine nucleoside analog antiviral drugs comprises valacyclovirhydrochloride.
 57. The treatment of claim 56 wherein: betweenapproximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered daily.
 58. The treatment of claim 57 wherein: approximately500 mg of valacyclovir hydrochloride are administered twice daily. 59.The method for treatment of claim 52 wherein: said member of thetetracycline family comprises minocycline hydrochloride.
 60. Thetreatment of claim 59 wherein: between approximately 50 to 200 mg ofminocycline hydrochloride are administered.
 61. The treatment of claim60 wherein: approximately 100 mg of minocycline hydrochloride areadministered twice daily.
 62. A method for medically treating thesymptoms of reactive arthritis or bursitis in humans comprising:administering to a patient an effective amount of the combination of amember of the family of synthetic purine nucleoside analog antiviraldrugs or a pharmaceutically acceptable ester or a metabolite thereof,and a member of the quinolone family or a metabolite thereof.
 63. Themethod for treatment of claim 62 wherein: said member of the family ofsynthetic purine nucleoside analog antiviral drugs comprises acyclovir.64. The treatment of claim 63 wherein: between approximately 100 mg to 4gm of acyclovir are administered.
 65. The treatment of claim 64 wherein:approximately 400 mg of acyclovir are administered twice daily.
 66. Themethod for treatment of claim 62 wherein: said member of the family ofsynthetic purine nucleoside analog antiviral drugs comprisesvalacyclovir hydrochloride.
 67. The treatment of claim 66 wherein:between approximately 125 mg to 4 gm of valacyclovir hydrochloride areadministered daily.
 68. The treatment of claim 67 wherein: approximately500 mg of valacyclovir hydrochloride are administered twice daily. 69.The method for treatment of claim 62 wherein: said member of thequinolone family comprises Ciprofloxacin.
 70. The treatment of claim 69wherein: between approximately 50 mg to 2 gm of Ciprofloxacin areadministered.
 71. The treatment of claim 70 wherein: approximately 500mg of Ciprofloxacin are administered twice daily.